This program project was started in September, 1982. It coordinates molecular biological, biochemical, physiological and pharmacological approaches to investigation of the role of vasoactive hormones and autacoids in circulatory homeostasis. The central theme of the program is the role of vasoactive systems (autocrine, paracrine, and endocrine) in the regulation of renal function and blood pressure (BP) and in the pathogenesis of hypertension. Major research emphasis is placed on the coordinated investigation of vasoactive hormones and autacoids. We postulate that a) vasodepressor autacoids such as kinins, endothelium- derived relaxing and contracting factors (EDRF and EDCF), and eicosanoids, in synergism with endocrine hormones such as atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), act by opposing hypertensive stimuli, and b) their blockade results in high BP or accelerated development of hypertension. specifically, we will investigate the role of kallikrein-kinin, SEV (which is a newly discovered member of the kallikrein family), renin-angiotensin, eicosanoids, EDRF, EDCF, ANF, and the effect of their inhibition and stimulation on: 1) BP, 2) renal blood flow and function, 3) vascular reactivity and tone, 4) microcirculation, 5) renal transport, 6) regulation of vascular smooth muscle function and growth, and 7) cardiac hypertrophy. These studies will be carried out both in normotensive animals and in different models of hypertension. this program project integrates the research activities and funding of the Hypertension and Vascular Research Division at Henry Ford Hospital. Four core units (Administrative, Radioimmunoassay, Biochemistry, and Biostatistics) will support and facilitate the scientific efforts of the investigators of the eight projects. Special expertise is centralized in the core units so that money, space, and equipment are used most efficiently. In addition, use of the core facilities removes the burden of day-to-day administrative and methodological concerns from project investigators, so that participants are free to spend their time and energy directly on their experiments. The scientists of the Hypertension and Vascular Research Division have created an exciting environment that is conducive to high-quality research. Since the inception of this program, significant advances have been made in determining the physiological and pathophysiological roles of vasoactive hormones and autacoids in the regulation of blood flow, renal function, BP and the pathogenesis of hypertension. The PPG provides a better integration of effort in which our continuing collaboration and sharing of ideas and expertise accelerates and acquisition of new knowledge about the role of humoral factors in circulatory homeostasis.